A substantial number of autoimmune diseases in mammals are associated with the expression of specific major histocompatability complex (MHC) subtype(s). For example, spondyloarthropathies are a group of inflammatory autoimmune diseases associated with human leukocyte antigen B27 (HLA-B27) expression. Spondyloarthropathies affect the sacroiliac joints, axial skeleton, and, to a lesser degree, peripheral joints and certain extra-articular organs. Common spondyloarthropathies include ankylosing spondylitis (AS), reactive arthritis (RA) (also known as Reiter's syndrome), psoriatic arthritis, undifferentiated spondyloarthropathy, and juvenile onset spondyloarthropathy (collectively termed the B27 diseases). A significant proportion of patients affected by spondyloarthropathies develop anterior uveitis, an autoreactive inflammation localized primarily to the anterior segment of the eye. Spondyloarthropathies and anterior uveitis appear to be triggered by certain bacteria, and are particularly prevalent in HLA-B27 positive individuals. For example, ankylosing spondylitis (AS) has a greater than 90% correspondence with the expression of HLA-B27.
The diagnosis of spondyloarthropathies and anterior uveitis relies predominantly on clinical and radiological criteria which are often unreliable and misdiagnosis is common. Treatments consist primarily of symptom-relieving drugs which have minimal effect on the underlying causes of the disease. Furthermore, effective preventative treatments for spondyloarthropathies and anterior uveitis are virtually non-existent.
There is a need for improved agents and methods for the treatment and/or prevention of HLA-associated diseases such as spondyloarthropathies and anterior uveitis. A need also exists for improved agents and methods to diagnose these diseases and identify individuals predisposed to developing them.